Editorial
Mechanism of in-stent restenosis after second-generation drug-eluting stents (DES): is it different from bare-metal stents and first-generation DES? Shoichi Kuramitsu, Shinichi Shirai, Kenji Ando Department of Cardiology, Kokura Memorial Hospital, Kitakyushu, Japan Correspondence to: Shoichi Kuramitsu, MD. Department of Cardiology, Kokura Memorial Hospital, 3-2-1 Asano, Kokurakita-ku, Kitakyushu, 8028555, Japan. Email: [email protected]. Submitted Nov 15, 2015. Accepted for publication Nov 23, 2015. doi: 10.3978/j.issn.2072-1439.2015.12.32 View this article at: http://dx.doi.org/10.3978/j.issn.2072-1439.2015.12.32
First-generation drug-eluting stents (DES) have dramatically reduced the rate of in-stent restenosis (ISR) and subsequent target lesion revascularization (TLR) compared with baremetal stents (BMS) (1). However, widespread use of firstgeneration DES has drawn attention to several unresolved, clinically relevant issues such as late stent thrombosis (ST) and late restenosis (2). Histopathological studies of firstgeneration DES have revealed that a chronic reaction to components of the permanent polymer reaction may lead to the delayed arterial healing, which is associated with increased risks of late DES failure (3,4). In addition, neoatherosclerosis is suggested as another cause of very late ST and late TLR (5). To overcome these limitations, biocompatible and biodegradable polymers have been developed and equipped with second-generation DES. Recent clinical trials demonstrated that second-generation DES has the improved efficacy and safety compared with those of first-generation DES (6,7). Nevertheless, secondgeneration DES, as well as first-generation DES, are not immune to ISR. In fact, Cassese et al. reported a large cohort of patients with angiographic surveillance that ISR rate of second-generation DES remains higher than 10% (8). Therefore, it is important to elucidate the mechanism of ISR after second-generation DES compared with that of BMS and first-generation DES, which may play a crucial role in the newly developed DES. In recent issue of American Journal of Cardiology, Goto et al. retrospectively analyzed intravascular ultrasound (IVUS) data in 298 ISR lesions (52 BMS, 138 firstgeneration DES, and 108 second-generation DES) to compare the mechanisms of ISR after second-generation
© Journal of Thoracic Disease. All rights reserved.
DES implantation with those of BMS and first-generation DES implantation (9). The main findings of this study was that (I) both neointimal hyperplasia (NIH) and stent underexpansion were the mechanisms of ISR even in the second-generation DES era; (II) NIH was dominant in 69% of BMS-ISR and 59% of DES-ISR; (III) stent underexpansion was greater in DES-ISR than BMS-ISR; (IV) stent fracture (SF) was found only in DES-ISR. NIH has emerged as the main cause of ISR in both BMS and first-generation DES (9-11). However, histopathological studies demonstrated considerable differences in the tissue characteristics of ISR between BMS and first-generation DES. BMS-ISR is typically characterized by NIH consisting of a proteoglycan matrix and high proportion of vascular smooth muscle cells. Conversely, DES-ISR is typically characterized by a proteoglycan-rich NIH with relatively few smooth muscle cells. Furthermore, neoatherosclerotic change within the restenostic tissue is seen earlier and more frequently in DES-ISR (5). In fact, an optical coherence tomography (OCT) study demonstrated that homogeneous and lipid-laden neointima were frequently observed in the BMS early phase (≤1 year) and late phase (>1 year), respectively; heterogeneous neointima was observed more frequently in the DES early phase (≤1 year) compared with the BMS early phase (44% vs. 9%, P5 years, without restenosis ≤1 year), whereas heterogeneous neointima was frequently observed in the late ISR (13). Furthermore, Habara also reported morphological differences of neointimal
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J Thorac Dis 2015;7(12):E599-E602
E600
characteristics between early (3 years) restenosis after first-generation DES implantation using OCT that thin-cap fibroatheroma-like and heterogeneous neointima were increased from early to very late phase (14). These findings are consistent with pathological findings. Therefore, NIH is the main cause of ISR in both BMS and first-generation DES, but the detailed mechanism of NIH may be different according to stent type and restenotic phase. Stent underexpansion is another mechanism of ISR in both BMS and first-generation DES. Previous IVUS studies showed that the cutoff of minimum stent area (MSA) to predict freedom from ISR was 6.5 mm2 for the BMS, 5.0 mm2 for sirolimus-eluting stent, and 5.7 mm2 for the paclitaxel-eluting stent (15,16). Recently, Song et al. reported the cutoff of MSA for the second-generation DES, demonstrating 5.4 mm2 for the everolimus-eluting stent and 5.3 mm2 for the zotarolims-eluting stent (17). These findings suggested that the cutoff of MSA for the second-generation DES was similar to that for the firstgeneration DES. Interestingly, Kang et al. showed that NIH was the dominant mechanism of ISR, whereas stent underexpansion associated with longer stent length (>28 mm) remained an important mechanism of ISR (11). In previous studies, stent underexpansion (NIH
Mechanism of in-stent restenosis after second-generation drug-eluting stents (DES): is it different from bare-metal stents and first-generation DES? Shoichi Kuramitsu, Shinichi Shirai, Kenji Ando Department of Cardiology, Kokura Memorial Hospital, Kitakyushu, Japan Correspondence to: Shoichi Kuramitsu, MD. Department of Cardiology, Kokura Memorial Hospital, 3-2-1 Asano, Kokurakita-ku, Kitakyushu, 8028555, Japan. Email: [email protected]. Submitted Nov 15, 2015. Accepted for publication Nov 23, 2015. doi: 10.3978/j.issn.2072-1439.2015.12.32 View this article at: http://dx.doi.org/10.3978/j.issn.2072-1439.2015.12.32
First-generation drug-eluting stents (DES) have dramatically reduced the rate of in-stent restenosis (ISR) and subsequent target lesion revascularization (TLR) compared with baremetal stents (BMS) (1). However, widespread use of firstgeneration DES has drawn attention to several unresolved, clinically relevant issues such as late stent thrombosis (ST) and late restenosis (2). Histopathological studies of firstgeneration DES have revealed that a chronic reaction to components of the permanent polymer reaction may lead to the delayed arterial healing, which is associated with increased risks of late DES failure (3,4). In addition, neoatherosclerosis is suggested as another cause of very late ST and late TLR (5). To overcome these limitations, biocompatible and biodegradable polymers have been developed and equipped with second-generation DES. Recent clinical trials demonstrated that second-generation DES has the improved efficacy and safety compared with those of first-generation DES (6,7). Nevertheless, secondgeneration DES, as well as first-generation DES, are not immune to ISR. In fact, Cassese et al. reported a large cohort of patients with angiographic surveillance that ISR rate of second-generation DES remains higher than 10% (8). Therefore, it is important to elucidate the mechanism of ISR after second-generation DES compared with that of BMS and first-generation DES, which may play a crucial role in the newly developed DES. In recent issue of American Journal of Cardiology, Goto et al. retrospectively analyzed intravascular ultrasound (IVUS) data in 298 ISR lesions (52 BMS, 138 firstgeneration DES, and 108 second-generation DES) to compare the mechanisms of ISR after second-generation
© Journal of Thoracic Disease. All rights reserved.
DES implantation with those of BMS and first-generation DES implantation (9). The main findings of this study was that (I) both neointimal hyperplasia (NIH) and stent underexpansion were the mechanisms of ISR even in the second-generation DES era; (II) NIH was dominant in 69% of BMS-ISR and 59% of DES-ISR; (III) stent underexpansion was greater in DES-ISR than BMS-ISR; (IV) stent fracture (SF) was found only in DES-ISR. NIH has emerged as the main cause of ISR in both BMS and first-generation DES (9-11). However, histopathological studies demonstrated considerable differences in the tissue characteristics of ISR between BMS and first-generation DES. BMS-ISR is typically characterized by NIH consisting of a proteoglycan matrix and high proportion of vascular smooth muscle cells. Conversely, DES-ISR is typically characterized by a proteoglycan-rich NIH with relatively few smooth muscle cells. Furthermore, neoatherosclerotic change within the restenostic tissue is seen earlier and more frequently in DES-ISR (5). In fact, an optical coherence tomography (OCT) study demonstrated that homogeneous and lipid-laden neointima were frequently observed in the BMS early phase (≤1 year) and late phase (>1 year), respectively; heterogeneous neointima was observed more frequently in the DES early phase (≤1 year) compared with the BMS early phase (44% vs. 9%, P5 years, without restenosis ≤1 year), whereas heterogeneous neointima was frequently observed in the late ISR (13). Furthermore, Habara also reported morphological differences of neointimal
www.jthoracdis.com
J Thorac Dis 2015;7(12):E599-E602
E600
characteristics between early (3 years) restenosis after first-generation DES implantation using OCT that thin-cap fibroatheroma-like and heterogeneous neointima were increased from early to very late phase (14). These findings are consistent with pathological findings. Therefore, NIH is the main cause of ISR in both BMS and first-generation DES, but the detailed mechanism of NIH may be different according to stent type and restenotic phase. Stent underexpansion is another mechanism of ISR in both BMS and first-generation DES. Previous IVUS studies showed that the cutoff of minimum stent area (MSA) to predict freedom from ISR was 6.5 mm2 for the BMS, 5.0 mm2 for sirolimus-eluting stent, and 5.7 mm2 for the paclitaxel-eluting stent (15,16). Recently, Song et al. reported the cutoff of MSA for the second-generation DES, demonstrating 5.4 mm2 for the everolimus-eluting stent and 5.3 mm2 for the zotarolims-eluting stent (17). These findings suggested that the cutoff of MSA for the second-generation DES was similar to that for the firstgeneration DES. Interestingly, Kang et al. showed that NIH was the dominant mechanism of ISR, whereas stent underexpansion associated with longer stent length (>28 mm) remained an important mechanism of ISR (11). In previous studies, stent underexpansion (NIH
